Two-Coordinate Thermally Activated Delayed Fluorescence Coinage Metal Complexes: Molecular Design, Photophysical Characters, and Device Application.

Since the emergence of the first green light emission from a fluorescent thin-film organic light emitting diode (OLED) in the mid-1980s, a global consumer market for OLED displays has flourished over the past few decades. This growth can primarily be attributed to the development of noble metal phosphorescent emitters that facilitated remarkable gains in electrical conversion efficiency, a broadened color gamut, and vibrant image quality for OLED displays. Despite these achievements, the limited abundance of noble metals in the Earth's crust has spurred ongoing efforts to discover cost-effective electroluminescent materials. One particularly promising avenue is the exploration of thermally activated delayed fluorescence (TADF), a mechanism with the potential to fully harness excitons in OLEDs. Recently, investigations have unveiled TADF in a series of two-coordinate coinage metal (Cu, Ag, and Au) complexes. These organometallic TADF materials exhibit distinctive behavior in comparison to their organic counterparts. They offer benefits such as tunable emissive colors, short TADF emission lifetimes, high luminescent quantum yields, and reasonable stability. Impressively, both vacuum-deposited and solution-processed OLEDs incorporating these materials have achieved outstanding performance. This review encompasses various facets on two-coordinate TADF coinage metal complexes, including molecular design, photophysical characterizations, elucidation of structure-property relationships, and OLED applications.

The small nucleolar RNA SnoR28 regulates plant growth and development by directing rRNA maturation.

Small nucleolar RNAs (snoRNAs) are noncoding RNAs (ncRNAs) that guide chemical modifications of structural RNAs, which are essential for ribosome assembly and function in eukaryotes. Although numerous snoRNAs have been identified in plants by high-throughput sequencing, the biological functions of most of these snoRNAs remain unclear. Here, we identified box C/D SnoR28.1s as important regulators of plant growth and development by screening a CRISPR/Cas9-generated ncRNA deletion mutant library in Arabidopsis thaliana. Deletion of the SnoR28.1 locus, which contains a cluster of three genes producing SnoR28.1s, resulted in defects in root and shoot growth. SnoR28.1s guide 2'-O-ribose methylation of 25S rRNA at G2396. SnoR28.1s facilitate proper and efficient pre-rRNA processing, as the SnoR28.1 deletion mutants also showed impaired ribosome assembly and function, which may account for the growth defects. SnoR28 contains a 7-bp antisense box, which is required for 2'-O-ribose methylation of 25S rRNA at G2396, and an 8-bp extra box that is complementary to a nearby rRNA methylation site and is partially responsible for methylation of G2396. Both of these motifs are required for proper and efficient pre-rRNA processing. Finally, we show that SnoR28.1s genetically interact with HIDDEN TREASURE2 and NUCLEOLIN1. Our results advance our understanding of the roles of snoRNAs in Arabidopsis.

Simultaneous Thermally Stimulated Delayed Phosphorescence (TSDP) and Thermally Activated Delayed Fluorescence (TADF) in a Two-Coordinated Au(I) Bimetallic Complex Featuring a Tandem Carbene Structure.

A bimetallic, two-coordinated carbene-metal-amine (cMa) Au(I) complex featuring a twisted tandem carbene structure (NHC1-Au-NHC2-Au-carbazolyl) was synthesized. The molecular structure in single crystals revealed a large dihedral angle between the two carbene ligands, while the bridged carbene NHC2 and carbazolyl (Cz) ligands were coplanar. A bluish green thermally stimulated delayed phosphorescence (TSDP) was observed in crystals with an emission lifetime over 70 µs, which can be attributed to the spin allowed diabatic population of a high-lying emissive triplet state from the 3LE characterized low-lying ones. The small rotation energy barrier of Cz along the coordination bond allowed conformers with large dihedral angles between NHC2 and Cz. The ICT characterized S1 state was consequently stabilized to achieve a thermally accessible energy gap to facilitate ISC between triplets and the S1, leading to the thermally activated delayed fluorescence (TADF). Simultaneous TSDP and TADF dual emission can be recorded in its doped polymer film owing to the coexistence of these different conformers.

Uveal melanoma distant metastasis prediction system: A retrospective observational study based on machine learning.

Uveal melanoma (UM) patients face a significant risk of distant metastasis, closely tied to a poor prognosis. Despite this, there is a dearth of research utilizing big data to predict UM distant metastasis. This study leveraged machine learning methods on the Surveillance, Epidemiology, and End Results (SEER) database to forecast the risk probability of distant metastasis. Therefore, the information on UM patients from the SEER database (2000-2020) was split into a 7:3 ratio training set and an internal test set based on distant metastasis presence. Univariate and multivariate logistic regression analyses assessed distant metastasis risk factors. Six machine learning methods constructed a predictive model post-feature variable selection. The model evaluation identified the multilayer perceptron (MLP) as optimal. Shapley additive explanations (SHAP) interpreted the chosen model. A web-based calculator personalized risk probabilities for UM patients. The results show that nine feature variables contributed to the machine learning model. The MLP model demonstrated superior predictive accuracy (Precision = 0.788; ROC AUC = 0.876; PR AUC = 0.788). Grade recode, age, primary site, time from diagnosis to treatment initiation, and total number of malignant tumors were identified as distant metastasis risk factors. Diagnostic method, laterality, rural-urban continuum code, and radiation recode emerged as protective factors. The developed web calculator utilizes the MLP model for personalized risk assessments. In conclusion, the MLP machine learning model emerges as the optimal tool for predicting distant metastasis in UM patients. This model facilitates personalized risk assessments, empowering early and tailored treatment strategies.

A long chain-induced depletion effect for abnormal grafting in the preparation of bimodal bidisperse polymer-grafted nanoparticles.

One of the challenging problems in the research field of polymer nanocomposites is how to prepare nanocomposites with high grafting density and strong ability of dispersion at the same time. For nanocomposites composed of bimodal bidisperse polymer chains and nanoparticles, the above requirements can be met by rationally adjusting the ratio of long and short polymer chains. In this study, the process of grafting bimodal bidisperse polymer chains onto the surface of nanoparticles in a grafting-to manner was investigated via computer simulation and theoretical methods. Three grafting strategies were designed: first short then long (SL) system, both short and long (Both) system and first long then short (LS) system. An abnormal phenomenon for the Both system was found by analyzing the grafting density of long and short polymer chains on the surface of nanoparticles. We speculate that the reason for this anomalous phenomenon is the "depletion effect" brought about by the long chains in the Both system. We employ the Polymer Reference Interaction Site Model (PRISM) theory to investigate this anomaly in-depth. By comparing the radial distribution function (RDF) predicted by the PRISM theory with the RDF results obtained by the molecular dynamics (MD) simulation, we found that with the increase of the number of long chains in the system, the grafting density of short polymer chains on the nanoparticle surface showed an obvious upward trend. The "depletion effect" brought by long chains was the main reason for higher short chains' grafting density of the Both system compared to the SL system. Our findings provide effective guidance for the design of nanoparticle-grafted bimodal bidisperse polymer chains and provide a theoretical basis for experimentation and production of polymer nanocomposites with better performance.

Prognosis of traumatic spinal cord injury in children: Follow-up of 86 patients.

PURPOSE: The long-term situation of children with spinal cord injury (SCI) was investigated, and suggestions for helping them better return to the society were provided. METHODS: SCI patients less than 18 years old hospitalized in Beijing Boai Hospital from January 2011 to December 2020 were retrospectively analyzed. Information including motor function, complications, characteristic changes, self-care abilities, school attendance and social participation were collected by telephone interview and electronic questionnaire. All the answers were statistically analyzed. RESULTS: A total of 86 cases were enrolled, 77 girls and 9 boys, with a median injury age of 6 years and 2 months. The follow-up time was 3-130 months. The main cause of trauma in these children was sport injury (66.3%), the thoracic spinal cord was involved the most (91.9%), and complete SCIs accounted for the majority (76.7%). In terms of complications, children with complete SCIs were more likely to have urinary incontinence, constipation and characteristic changes (p < 0.05); whereas the incomplete SCIs often have spasticity (p < 0.05). As to the daily living abilities, children with incomplete lumbar SCIs were more capable to accomplish personal hygiene, transfer, and bathing independently than those with complete injuries, or cervical/thoracic SCIs, respectively (p < 0.05). Moreover, children older than 9 years care more able to dress and transfer independently than the youngers (p < 0.05). Wheelchair users accounted for 84.9% and more than half of them were able to propel wheelchair independently, and those who move passively in wheelchairs were mostly introverted kids (p < 0.05). Almost all (93.8%) children with incomplete injuries were able to walk independently. Most (79.1%) children continued to attending school, and 41.9% participated in interest classes. Unfortunately, 67.4% of the children spent less time playing with their peers than before the injury. CONCLUSION: SCIs impair physical structures and function of children, affect their independence in daily living, and restrict school attendance and social interaction. Comprehensive rehabilitation after injury is a systematic work. Medical staff and caregivers should not only pay attention to neurological function, but also help them improve self-care abilities. It is also important to balance rehabilitation training and school work and social participation.

[Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi].

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.

SNP rs7130280 in lncRNA NONHSAT159216.1 confers susceptibility to Behçet's disease uveitis in a Chinese Han population.

OBJECTIVE: Long noncoding RNA (lncRNA) plays a crucial role in the process of immune-mediated diseases. However, the defined involvement of lncRNA on Behçet's disease (BD) is not well known. The aim of this study was to investigate the effects of lncRNA-related single nucleotide polymorphisms (SNPs) on BD susceptibility in Chinese populations. METHODS: A two-stage case-control association study was conducted in a cohort of 1152 BD individuals and 1152 healthy controls. Genotyping was performed by a MassARRAY System. Quantified expression of the lncRNA-miRNA-mRNA molecular axis was detected by real-time PCR and western blot. The cell proliferation was measured by CCK-8 assay. RESULTS: Two-stage association analysis showed a significantly decreased frequency of A allele of SNP rs7130280 in BD patients compared with healthy controls [OR 0.72 (95% CI 0.64, 0.81), Pc = 1.15 × 10-6]. Functionally, SNP rs7130280 could influence the secondary structure and relative expression of NONHSAT159216.1 in human THP-1/U937 macrophages and in peripheral blood mononuclear cells from healthy volunteers. In vitro, overexpression of the rs7130280 A allele also suppressed cell proliferation. Mechanistically, rs7130280 A allele could inhibit the expression of miR-6778-5p, thus enhancing its downstream molecular RPS6KA4/IL10 in a competing endogenous RNA sponge manner. CONCLUSION: Our findings suggest that NONHSAT159216.1 rs7130280 G>A might be associated with a low risk of BD and participates in a potential lncRNA-miRNA-mRNA regulatory network.

[Influence of Pain-depression Comorbidity on Quality of Life in Patients with Neuromyelitis Optica Spectrum Disorder].

Objective To investigate the incidence,treatment,therapeutic effect,and impact on quality of life of pain-depression comorbidity in the patients with neuromyelitis optica spectrum disorder(NMOSD).Methods The NMOSD patients comorbid with pain visiting the out-patient clinic of Peking Union Medical College Hospital were interviewed in a face-to-face manner by neurologists for evaluating the neurologic disease.Pain,depression,and quality of life were evaluated by anesthesiologists based on the brief pain inventory,the Beck depression inventory-Ⅱ,and the MOS 36-item short form health survey scales,respectively.Results Totally 81 patients were included in this study,among which 38(46.9%)patients comorbid with depression were enrolled in the comorbidity group.The pain severity showed no significant difference between the two groups(3.3±3.1 vs. 2.3±2.2,P=0.087).The daily life activities and health-related quality of life were more severely influenced in the patients with comorbidity than in the patients without comorbidity as illustrated by the breif pain inventory[general activity and normal work(P=0.001);mood,relationship with other people,and enjoyment of life(all P<0.001);walking ability(P=0.004);sleep(P=0.016)]and the MOS 36-item short form health survey scales[physical functioning(P=0.001);role-physical,bodily pain,general health,vitality,social functioning,role-emotional,mental health(all P<0.001)].Only 30.9% of pain sufferers received analgesic medications,with the mean pain reduction percentage of(53.6±28.9)%.None of the patients in this study took antidepressants.Conclusions Pain-depression comorbidity was common in NMOSD patients and severely influenced the quality of life of the patients.However,only a few patients received analgesic or antidepressant medications.Pain-depression comorbidity in NMOSD patients should be scrutinized.

Increased sagittal diameter of the vertebral arch aids in diagnosis of lumbar spondylolysis.

OBJECTIVE: To identify a diagnostic indicator of lumbar spondylolysis visible in plain X-ray films. METHODS: One hundred and seventy-two patients with low back pain who received X-ray and computerized tomography (CT) examinations were identified and studied. They were divided into three groups: the spondylosis without spondylolisthesis (SWS) group, comprising 67 patients with bilateral pars interarticularis defects at L5 and without spondylolisthesis, the isthmic spondylolisthesis (IS) group, comprising 74 patients with L5/S1 spondylolisthesis and bilateral L5 pars interarticularis defects, and the control group, comprising 31 patients with low back pain but without spondylolysis. The sagittal diameters of the vertebral arch (SDVAs) of L4 and L5 were measured in lateral X-ray image, and the differences in SDVA between L4 and L5 (DSL4-5) in each case were calculated and analyzed. RESULTS: There were no significant differences in demographic characteristics among the three groups. In the SWS and IS groups, the SDVA of L5 was significantly longer than the SDVA of L4 (p < 0.001), whereas no significant difference found in the control group (p > 0.05). DSL4-5, in which the SDVA of L4 was subtracted from the SDVA of L5, significantly differed among the three groups (p < 0.001), and the normal threshold was provisionally determined to be 1.55 mm. CONCLUSIONS: In bilateral L5 spondylolysis, the SDVA of L5 is wider than the SDVA of L4, and this difference is greater in isthmic spondylolisthesis. This sign in lateral X-rays may provide a simple and convenient aid for the diagnosis of spondylolysis.

Synthesis of Polymer Single-Chain Nanoparticle with High Compactness in Cosolvent Condition: A Computer Simulation Study.

Polymeric single-chain nanoparticles (SCNPs) are soft nano-objects synthesized by intramolecular crosslinking of isolated single polymer chains. Syntheses of such SCNPs usually need to be performed in a dilute solution. In such a condition, the bonding probability of the two active crosslinking units at a short contour distance along the chain backbone is much higher than those which are far away from each other. Such a reaction condition often results in local spheroidization and, therefore, the formation of loosely packed structures. How to inhibit the local spheroidization and improve the compactness of SCNPs is thus a major challenge for the syntheses of SCNPs. In this study, computer simulations are performed and the fact that a precollapse of the polymer chain conformation in a cosolvent condition can largely improve the probability of the crosslinking reactions at large contour distances is demonstrated, favoring the formations of closely packed globular structures. As a result, the formed SCNPs can be more spherical and have higher compactness than those fabricated in ultradilute good solvent solution in a conventional way. It is believed this simulation work can provide a insight into the effective syntheses of SCNPs with spherical conformations and high compactness.

Ischemic damage may play an important role in spinal cord injury during dancing.

STUDY DESIGN: Retrospective analysis. SETTING: China Rehabilitation Research Center, Beijing, China. OBJECTIVE: To explore possible mechanisms underlying spinal cord injury (SCI) in children caused by hyperextension of the spine while dancing. METHODS: The clinical records of 88 children with SCI (mean age, 5.97 years; age range, 4-10 years) admitted to our hospital from January 1989 to October 2019 were retrospectively reviewed. Computed tomography and magnetic resonance imaging were performed on the day of injury. The time from injury to development of paralysis, as well as post-injury activities were surveyed, while abnormal patterns on images, the range of the involved vertebrae, and the extents of edema and atrophy were assessed. RESULTS: Among the 88 patients, 6 (6.8%) were unable to move immediately after SCI, while paralysis occurred in 42, 23, and 17 patients at <30, 30-60, and >60 min after SCI, respectively. The neurological level of injury of 84 patients was between T4 and T12. On sagittal T2-weighted images (T2WIs), the longitudinal range of spinal cord edema was more than one vertebral body in 65 patients, while spinal cord atrophy below T8 was found in 40 patients. On axial T2WIs, although three patients had none, long T2 signals were found in the central gray matter of seven patients. Meanwhile, necrosis of the central area combined with the peripheral white matter was observed in 57 patients, while three patients had total involvement on a cross section. CONCLUSION: Ischemia-related damage, rather than direct trauma to the spinal cord, may play an important role in SCI due to spinal hyperextension during dancing.

A simulation study on the glass transition behavior and relevant segmental dynamics in free-standing polymer nanocomposite films.

In polymer/nanoparticle composite (PNC) thin films, polymer chains experience strong confinement effects not only at the free surface area but also from nanoparticles (NPs). In this work, the influence of NP-polymer interaction and NP distribution on the polymer segmental dynamics and the glass transition behavior of PNC free-standing films are investigated through molecular dynamics simulations. We demonstrate that NPs will migrate to the film surface area and form an NP-concentrated layer when NP-polymer interactions are weak, while NPs are well dispersed in the bulk region when NP-polymer interactions are strong. In both cases, we find increases in the glass transition temperature Tg compared with the pure film without NPs, although with a different degree. The weakly interacting system has the same Tg as the pure bulk system without NPs. The NP layer formed at the surface area reduces both the mobility of the surface polymer beads and the mobility gradient in the film normal direction (MGFND), therefore resulting in an increase in the Tg which highlights the vital role of the mobile surface layer. In contrast, the NPs in the bulk region enlarge the MGFND. NPs have opposite influences on the polymer bead dynamic anisotropy when they interact weakly or strongly with polymers, weakened for the former and enhanced for the latter. These findings offer a clear picture of the segmental dynamics and glass transition behavior in free-standing PNC films with different NP-polymer interaction strengths. We hope these results will be helpful for the property design of related materials.

A comparative study on the dynamic heterogeneity of supercooled polymers under nanoconfinement.

Dynamic heterogeneity (DH) is a universal property of glass transition phenomena. In this work, we perform a comparative analysis of DH for pure polymer and polymer/nanoparticle composite systems in both film and bulk states via molecular dynamics simulations. We find that the dynamic gradient and the faster average dynamics due to the presence of a free surface are two leading factors, resulting from a nanoconfinement effect, which influence different parts of DH in a film system. The dynamic gradient results from differences in dynamics at different distances from the mobile surface, which induces a large deviation from the Gaussian distribution for the displacement distribution in the film. At the same time, the maximum string size which describes the region size for cooperative motion (dynamic correlation) can also be influenced by the dynamic gradient, although this influence is much weaker than that on the displacement distribution. On the other hand, reflecting temporal fluctuations of dynamics or temporal parts of DH, characteristic peak times of the non-Gaussian parameter and string size, and the ratio between persistent times and exchange times which describe the dynamic exchange properties, are mainly influenced by the faster dynamics on average. Our results demonstrate that measuring different properties (dynamic distribution, dynamic correlation or dynamic exchange) place an emphasis on distinct temporal and spatial parts of DH. It is necessary to use combinational measurements of these properties to give a complete picture of DH in nanoconfinement environments.

Dynamics and reaction kinetics of coarse-grained bulk vitrimers: a molecular dynamics study.

Vitrimers with dynamic covalent bonds make thermosetting materials plastic, recyclable and self-repairing, and have broad application prospects. However, due to the complex composition of vitrimers and the dynamic bond exchange reactions (BERs), the mechanism behind their unique dynamic behavior is not fully understood. We used the hybrid molecular dynamics-Monte Carlo (MD-MC) algorithm to establish a molecular dynamics model that can accurately reflect BERs, and reveal the intrinsic mechanism of the dynamic behavior of the vitrimer system. The simulation results show that BERs change the diffusion mode of the vitrimer's constituent molecules, which in turn affects the BER and other relaxation dynamics. This provides a theoretical basis and a specific method for the rational design of the rheological properties of vitrimers.

Heterogeneity among traumatic spinal cord injuries at the thoracolumbar junction: helping select patients for clinical trials.

STUDY DESIGN: Retrospective analysis. SETTING: China Rehabilitation Research Center, Beijing, China. OBJECTIVE: A retrospective study that documents the modalities and clarifies the heterogeneity among spinal cord injuries (SCIs) caused by trauma to the thoracolumbar vertebral junction. METHODS: X-ray and MRI imaging, neurological records, and the urodynamics results of 190 patients were reviewed and used to categorize different SCI modalities. First, injuries were divided into complete and incomplete injuries using the International Standard for Neurological Classification of Spinal Cord Injury. Next, the complete injuries were further grouped using the neurological level of injury and Long T2 signal from mid-sagittal MRI images, whereas the bulboconvernosus reflexes were also used as a reference to detect injury to the sacral cord. RESULTS: The SCI modalities were classified into five categories: pure complete epiconus lesion with caudal cord intact (G1), complete epiconus injury with conus medullaris (CM) totally involved in the lesion (G2), CM syndrome, cauda equine syndrome without sacral sparing (G3 and G4), and incomplete injury (G5). CONCLUSIONS: The heterogeneity of SCIs at the thoracolumbar junction was documented, a criterion we propose to be of great significance when selecting patients for clinical trials. In particular, the G2 group, which comprises nearly one third of the patients with epiconus lesions, is sometimes mistaken as G1, an observation that has thus far received insufficient attention.

System-Pharmacology Dissection of Traditional Chinese herbs SINI Decoction for Treatment of Cardiovascular Diseases.

Abstract: Cardiovascular diseases (CVDs) are leading causes of death in the world, owing to noticeable incidence and mortality. Traditional Chinese Medicine (TCM) SINI Decoction (SND) is used to prevent and treat CVDs, which has attracted extensive attention for its moderate and little side effects. However, the involved molecular mechanisms are exceedingly complicated and remain unclear. Systems pharmacology, as a novel approach that integrates systems biology and pharmacology plays a significant role in investigating the molecular mechanism of TCM. In systems pharmacology approach, we use to systematically uncover the mechanisms of action in Chinese medicinal formula SND as an effective treatment for CVDs, which mainly includes:1) molecular database building; 2) ADME evaluation; 3) target-fishing 4) network construction and analysis. The results show that 78 underlying valid ingredients and their corresponding 71 direct targets of SND were obtained. And SND take part in cardiomyocyte protection, blood pressure regulation, and lipid regulation module in treatment of CVDs by cooperative way. Systems pharmacology as an emerging field that investigates the molecular mechanisms of TCM through pharmacokinetic evaluation target prediction, and pathway analysis, which will facilitate the development of traditional Chinese herbs in modern medicine.

GAS5 silencing protects against hypoxia/ischemia-induced neonatal brain injury.

Hypoxic/ischemic brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. However, the molecular mechanism of HIBD in the neonatal infant is still elusive. Long non-coding RNAs are shown as important regulators of brain development and many neurological diseases. Here, we determined the role of long noncoding RNA-GAS5 in HIBD. GAS5 expression was significantly up-regulated in hypoxic/ischemic-injured neonatal brain and hippocampal neurons. GAS5 silencing protected against hypoxic/ischemic-induced brain injury in vivo and primary hippocampal neuron injury in vitro. Mechanistically, GAS5 regulated hippocampal neuron function by sponging miR-23a. Intracerebroventricular injection of GAS5 shRNA significantly decreased brain GAS5 expression, reduced brain infarct size, and improved neurological function recovery. Collectively, this study suggests a promising therapeutic approach of GAS5 inhibition in the treatment of neonatal HIBD.

High Prevalence of HBV Lamivudine-Resistant Mutations in HBV/HIV Co-Infected Patients on Antiretroviral Therapy in the Area with the Highest Prevalence of HIV/HBV Co-Infection in China.

OBJECTIVES: We aimed to determine the prevalence of hepatitis B virus (HBV) drug-resistant mutations in patients co- infected with HBV/human immunodeficiency virus (HIV), including both drug-naïve subjects and those who received antiretroviral therapy (ART) in Guangxi, where the prevalence of HIV/HBV co-infection is highest in China. METHODS: Two hundred and three subjects co-infected with HBV/HIV were recruited, including 123 drug-naïve patients (group 1) and 80 who received ART (group 2). The polymerase gene of HBV in the serum of all study subjects was analysed. RESULTS: The results showed that the prevalence of HBV drug-resistant mutations in group 2 (76.5%, 95% CI 56.3-96.7) was significantly higher than that in group 1 (1.4%, 95% CI -1.4 to 4.2; χ2 = 50.955, p < 0.05). The major pattern of lamivudine (3TC)-resistant mutations is L180M+M204I+L80I (35.7%). In total, 95% of subjects with resistant mutations had cross-resistance to telbivudine and entecavir. No putative tenofovir disoproxil fumarate (TDF) resistance change was found. Five subjects (6.5%) in group 2 had HBV viral loads over 10 × 106 copies/mL. Four of them had 3TC-resistant mutations. Multivariate analysis showed that ART was the only factor associated with the development of drug-resistant mutations. CONCLUSION: Treating HIV in HIV/HBV co-infection with antiretroviral agents may result in a very high prevalence of HBV 3TC-resistant mutations. TDF could not completely suppress HBV replication.